Clinical, immunological and genetic characteristic of patients with clinical phenotype associated to LRBA-deficiency in Colombia / Características clínicas, inmunológicas y genéticas de pacientes con el fenotipo asociado a deficiencia LRBA en Colombia

Abstract Background: LPS-responsive beige -like anchor protein (LRBA) deficiency is a primary immunodeficiency disease caused by loss of LRBA protein expression, due to biallelic mutations in LRBA gene. LRBA deficiency patients exhibit a clinically heterogeneous syndrome. The main clinical complication of LRBA deficiency is immune dysregulation. Furthermore, hypogammaglobulinemia is found in more than half of patients with LRBA-deficiency. To date, no patients with this condition have been reported in Colombia Objective: To evaluate the expression of the LRBA protein in patients from Colombia with clinical phenotype associated to LRBA-deficiency. Methods: In the present study the LRBA-expression in patients from Colombia with clinical phenotype associated to LRBA-deficiency was evaluated. After then, the clinical, the immunological characteristics and the possible genetic variants in LRBA or other genes associated with the immune system in patients that exhibit decrease protein expression was evaluated. Results: In total, 112 patients with different clinical manifestations associated to the clinical LRBA phenotype were evaluated. The LRBA expression varies greatly between different healthy donors and patients. Despite the great variability in the LRBA expression, six patients with a decrease in LRBA protein expression were observed. However, no pathogenic or possible pathogenic biallelic variants in LRBA, or in genes related with the immune system were found. Conclusion: LRBA expression varies greatly between different healthy donors and patients. Reduction LRBA-expression in 6 patients without homozygous mutations in LRBA or in associated genes with the immune system was observed. These results suggest the other genetic, epigenetic or environmental mechanisms, that might be regulated the LRBA-expression.

Resumen Antecedentes: la deficiencia de LRBA (del inglés, LPS-responsive beige -like anchor protein) es una inmunodeficiencia primaria causada por la pérdida de la expresión de la proteína LRBA, debido a mutaciones bialélicas en el gen LRBA. Los pacientes con deficiencia de LRBA exhiben un síndrome clínicamente heterogéneo. La principal complicación clínica de la deficiencia de LRBA es la desregulación inmune. Además, la hipogammaglobulinemia se encuentra en más de la mitad de los pacientes con deficiencia de LRBA. Hasta la fecha, no se han reportado pacientes con esta afección en Colombia Objetivo: Evaluar la expresión de la proteína LRBA en pacientes de Colombia con fenotipo clínico asociado a deficiencia de LRBA Métodos: En el presente estudio se evaluó la expresión de LRBA en pacientes de Colombia con fenotipo clínico asociado a deficiencia de LRBA. Después de eso, se evaluaron las características clínicas, inmunológicas y las posibles variantes genéticas en LRBA o en otros genes asociadados con el sistema inmune en pacientes que exhiben una disminución de la expresión de la proteína. Resultados: En total, se evaluaron 112 pacientes con diferentes manifestaciones clínicas asociadas al fenotipo clínico LRBA. La expresión de LRBA varía mucho entre diferentes donantes sanos y pacientes. A pesar de la gran variabilidad en la expresión de LRBA, se observaron seis pacientes con una disminución en la expresión de la proteína LRBA. Sin embargo, no se encontraron variantes bialélicas patógenas o posibles patógenas en LRBA, o en genes relacionados con el sistema inmune. Conclusión: La expresión de LRBA varía mucho entre diferentes donantes sanos y pacientes. Se observó reducción de la expresión de LRBA en 6 pacientes sin mutaciones homocigotas en LRBA o en genes asociados. Estos resultados sugieren los otros mecanismos genéticos, por ejemplo epigenéticos o ambientales, que podrían estar regulados por la expresión de LRBA

Severe Hypogammaglobulinemia Associated with Active Lupus Nephritis Treatment Resulting in Cytomegalovirus Infection

Patients with severe active lupus nephritis (LN) require immunosuppressive therapy to induce remission. However, the development of profound hypogammaglobulinemia causing cytomegalovirus (CMV) disease is a rare occurrence during standard immunotherapy. A 27-year-old woman who presented with active LN along with moderate renal impairment was treated with of mycophenolate mofetil (MMF) and methylprednisolone. MMF was soon switched with low-dose intravenous (IV) cyclophosphamide (CYC) owing to the development of posterior reversible encephalopathy syndrome and deterioration of renal function requiring hemodialysis. After two cycles of IV CYC, she developed CMV colitis and pneumonia. Although her serum immunoglobulin (Ig) concentrations before receiving immunosuppressive treatment were normal, they were profoundly reduced at CMV disease onset and continued to maintain low level for 30 months. Severe hypogammaglobulinemia can occur during standard therapy for LN, especially in patients with impaired renal function, pointing out the importance of close monitoring of Ig levels and CMV infection.

Hypogammaglobulinemia: a diagnosis that must not be overlooked

Humoral immunological defects are frequent and important causes of hypogammaglobulinemia, leading to recurrent infections, autoimmunity, allergies, and neoplasias. Usually, its onset occurs in childhood or during the second and third decades of life; however, the diagnosis is made, on average, 6 to 7 years afterwards. As a consequence, antibody defects can lead to sequelae. Here we describe the clinical-laboratory characteristics, treatment, and prognoses of patients with hypogammaglobulinemia. An observational, cross-sectional, and retrospective study of patients attending the recently established outpatient group of Clinical Immunology between 2013 and 2018 was carried out. Patients with IgG levels below 2 standard deviations from the mean values for the age and/or impaired antibody response were included. Eight patients (3 F and 5 M; median age=41 years (16-65), average symptom onset at 25 years (1-59), and time to diagnosis of 10 years were included. The main infections were: sinusitis in 7/8, pneumonia in 6/8, otitis in 2/8, tonsillitis and diarrhea in 2/8, and diarrhea in 2/8 patients. Hypothyroidism was identified in 4/8 (50%) patients. Rhinitis was found in 7/8 (87.5%) and asthma in 3/8 (37.5%) patients. The tomographic findings were consolidations, atelectasis, emphysema, ground glass opacity, budding tree, bronchial thickening, and bronchiectasis. Immunoglobulin reposition was used between 466 and 600 mg/kg monthly (514.3 mg·kg-1·dose-1). Prophylactic antibiotic therapy was included in 7/8 (87.5%) patients. Airway manifestations prevailed in patients with hypogammaglobulinemia. There is a need for educational work to reduce the time of diagnosis and initiation of treatment, avoiding sequelae.

A propósito de un caso: enfermedad de Kawasaki incompleta en un niño con hipogammaglobulinemia / A case report: incomplete Kawasaki disease in a hypogammaglobulinemic child

La enfermedad de Kawasaki (EK) es una vasculitis autoinmunitaria sistémica que afecta a los vasos pequeños y medianos. La complicación principal de la enfermedad de Kawasaki es el aneurisma de las arterias coronarias, cuyo riesgo es más alto si se retrasa el diagnóstico y el tratamiento. Si bien hasta la fecha se han presentado casos de EK completa e incompleta en diferentes tipos de enfermedades por inmunodeficiencia, no se ha informado acerca de la evolución clínica de la EK en pacientes con hipogammaglobulinemia (HG). En este artículo, se presenta un caso de diagnóstico de EK incompleta en un niño con HG transitoria de la infancia. También se resumen casos previamente informados de EK e inmunodeficiencia. En el caso de una inmunodeficiencia, las infecciones recurrentes pueden ocultar la EK, lo que retrasa el diagnóstico y aumenta el riesgo de complicaciones. En pacientes inmunodeficientes, debe tenerse en cuenta la posibilidad de EK cuando la fiebre es prolongada.

Kawasaki Disease (KD) is a systemic autoimmune vasculitis that affects small and medium sized vessels. Main complication of Kawasaki Disease is coronary artery aneurism, which has higher risk in case of delayed diagnosis and treatment. Although, complete and incomplete KD cases in different types of immune deficiency diseases have been presented up to date, clinical course of KD in patients with hypogammaglobulinemia (HG) has not been reported. Herein, a case diagnosed as incomplete KD in a child with transient HG of infancy has been reported. Previously reported cases with KD and immunedeficiency have also been summarized. Recurrent infections in case of immunedeficiency may mask KD disease resulting in delay in diagnosis and increased risk of complication. KD should be kept in mind in immunedeficient patients in case of prolonged fever.

Evaluación de la zona gamma del proteinograma por electroforesis: correspondencia clínico-patológica / Evaluation of protein electrophoresis in the gamma zone: clinicopathological correspondence / Avaliação da área gamma do proteinograma por eletroforese: correspondência clínico-patológica

El proteinograma por electroforesis (PxE) sérico es solicitado para detectar modificaciones del perfil proteico. El objetivo del trabajo fue evaluar las alteraciones de la zona gammaglobulina y su correspondencia con distintos estados clínico-patológicos. Se incluyeron 7.259 pacientes (1-89 años) a los que en 2013 se les solicitó PxE. Según el trazado densitométrico, en la zona gammaglobulina se reconocieron diferentes grupos: hipogammaglobulinemia (<0,60 g/dL), hipergammaglobulinemia policlonal (≥1,80 g/dL), banda monoclonal (BM) y bandas oligoclonales. Prevaleció la hipergammaglobulinemia policlonal (4,2%), seguida por BM (1,4%) e hipogammaglobulinemia (0,8%). Hipergammaglobulinemia policlonal (>3 g/dL) se observó en: hepatitis autoinmune, cirrosis, síndrome de Sjögren, enfermedad mixta del tejido conectivo, HIV, hepatitis C y enfermedad de Castleman. El hallazgo de BM correspondió a 47% de pacientes con gammapatía monoclonal de significado incierto y 40% con mieloma múltiple; el 0,5% fueron casos nuevos. Con hipogammaglobulinemias, en adultos prevaleció la inmunosupresión terapéutica (55%), seguida por diabetes/síndrome metabólico/hipotiroidismo (23%); en niños, 22% por inmunosupresión y 78% con hipogammaglobulinemia no clasificada como inmunodeficiencia primaria. Se concluye que en 6,4% de los PxE se observó alteración de la zona gammaglobulina; prevaleció la hipergammaglobulinemia policlonal. En 1 de cada 200 PxE se pesquisó un paciente con BM. El hallazgo de hipergammaglobulinemia policlonal o BM se correspondió con distintos estados clínico-patológicos.

Serum protein electrophoresis (PEP) is requested to screen changes in the protein profile. The aim of this study was to evaluate alterations in the gamma globulin zone and correspondence with various clinical and pathological states. 7259 patients were included (1-89 years of age) who had been requested a PEP in 2013. According to the densitometric tracing, in the gamma globulin zone different groups were recognized: hypogammaglobulinemia (<0.60 g/dL), polyclonal hypergammaglobulinemia (≥1,80 g/dL), monoclonal band (MB) and oligoclonal band. The polyclonal hypergammaglobulinemia prevailed (4.2%), followed by MB (1.4%) and hypogammaglobulinemia (0.8%). Polyclonal hypergammaglobulinemia (>3 g/dL) was observed in autoimmune hepatitis, alcoholic cirrhosis, Sjögren's syndrome, mixed connective tissue disease, HIV, hepatitis C and Castleman's disease. The MB finding corresponded to a 47% of patients with monoclonal gammopathy of undetermined significance and 40% with multiple myeloma; 0.5% were new cases. In adults, hipogammaglobulinemias prevailed in therapeutic immunosuppression cases (55%), followed by patients with diabetes/ metabolic syndrome/ hypothyroidism (23%); in children, 22% with immunosuppression and 78% corresponded to hipogammaglobulinemias not classified as primary immunodeficiency. To conclude, an alteration in the gamma globulin zone was observed in 6.4% of PEP. In 1 out of 200 PEP MB was found. The finding of polyclonal hypergammaglobulinemia or MB corresponded to different clinicopathological states.

O proteinograma por eletroforese (PXE) sérico é solicitado para detectar modificações no perfil proteíco. O objetivo do trabalho foi avaliar as alterações da área gammaglobulina e sua correspondência com diversos estados clínico-patológicos. Incluíram-se 7259 pacientes (1-89 anos) aos quais, em 2013, foi solicitado um PxE. De acordo com o traçado densitométrico, na área gammaglobulina, diferente grupos foram reconhecidos: hipogammaglobulinemia (<0,60 g/dL), hipergammaglobulinemia policlonal (≥1,80 g/dL), banda monoclonal (BM) e bandas oligoclonais. Prevaleceu a hipergammaglobulinemia policlonal (4,2%), seguida por BM (1,4%) e hipogammaglobulinemia (0,8%). Hipergammaglobulinemia policlonal (>3 g/dL) foi observada em: Hepatite autoimune, cirrose, síndrome de Sjögren, doença mista do tecido conjuntivo, HIV, hepatite C e doença de Castleman. O achado de BM correspondeu a 47% de pacientes com gammapatia monoclonal de significado indeterminado e 40% com mieloma múltiplo; 0,5% eram casos novos. Com hipogammaglobulinemias em adultos prevaleceu a imunossupressão terapêutica (55%), seguida por diabete/síndrome metabólica/hipotireoidismo (23%); em crianças, 22% por imunossupressão e 78% com hipogammaglobulinemia não classificados como imunodeficiência primária. Conclui-se que em 6,4% dos PxE foi observada alteração da área gammaglobulina; prevaleceu a hipergammaglobulinemia policlonal. Em 1 de cada 200 PxE foi encontrado um paciente com BM. O achado de hipergammaglobulinemia policlonal ou BM se correspondeu com diferentes estados clínico-patológicos.

Pure Red Cell Aplasia Associated with Good Syndrome

Pure red cell aplasia (PRCA) and hypogammaglobulinemia are paraneoplastic syndromes that are rarer than myasthenia gravis in patients with thymoma. Good syndrome coexisting with PRCA is an extremely rare pathology. We report the case of a 50-year-old man with thymoma and PRCA associated with Good syndrome who achieved complete PRCA remission after thymectomy and postoperative immunosuppressive therapy, and provide a review of the pertinent literature.

Rituximab e hipogammaglobulinemia / Rituximab and hypogammaglobulinemia

El rituximab (RTX), un anticuerpo quimérico anti-CD20 que induce la depleción de linfocitos B, es utilizado para el tratamiento de enfermedades linfoproliferativas y autoinmunes. La inmunodeficiencia humoral relacionada al tratamiento con RTX comenzó a ser un motivo de derivación a nuestro Servicio, por lo que decidimos analizar a los pacientes con el antecedente de haber sido tratados con RTX que consultaron por hipogammaglobulinemia o infecciones recurrentes desde noviembre de 2010 hasta diciembre de 2014. Evaluamos a ocho pacientes, siete mujeres y un varón. El tiempo promedio de seguimiento fue de 19.3 ± 18.8 meses, rango 1 a 54, con una mediana de 13. Tres tenían proteinogramas normales previo a la administración de RTX, tres hipogammaglobulinemia, y de dos no hay datos. A ninguno se le realizó una determinación cuantitativa de inmunoglobulinas previa al tratamiento. Cuatro recibieron RTX por linfoma B no Hodgkin, dos por leucemia linfocítica crónica, uno por púrpura trombocitopénica autoinmune y otro por poliangeítis microscópica. A seis se les diagnosticó hipogammaglobulinemia y a uno deficiencia de IgM, IgA e IgG2. Cinco presentaron infecciones, cuatro con buena respuesta al tratamiento de reemplazo con gammaglobulina. La inmunodeficiencia humoral relacionada a RTX es una causa de consulta cada vez más frecuente. Resulta fundamental disponer de los niveles de inmunoglobulinas previo al inicio de su administración para poder establecer una relación etiológica y durante el seguimiento, para disminuir el retraso diagnóstico. El tratamiento con gammaglobulina en dosis sustitutivas parece ser de utilidad en pacientes con infecciones graves o recurrentes.

Rituximab, a chimeric monoclonal antibody against CD20, induces the depletion of B lymphocytes. It is used for the treatment of lymphoproliferative and autoimmune diseases. Antibody immunodeficiency associated to RTX treatment is a new motif for consultation to our service. We decided to study those patients that having been treated with RTX, consulted for hypogammaglobulinemia or recurrent infections between November 2010 and December 2014. We evaluated eight patients, seven female and one male. The average follow up time was 19.3 ± 18.8 months, range 1 to 54, median 13. Three had a normal electrophoretic proteinogram before receiving RTX, three had hypogammaglobulinemia and in two data was not available. None of them had a quantitative determination of immunoglobulins before receiving RTX. Four received RTX as a treatment of non Hodking lymphoma, two as a treatment of chronic lymphocytic leukemia, one for immune thrombocytopenic purpura and other for microscopic polyangiitis. Six were diagnosed with hypogammaglobulinemia and one with combined IgM, IgA and IgG2 deficiency. Five presented infections, four of them with good response to intravenous immunoglobulin. RTX related antibody deficiency consultations are increasing. It is important to determine the immunoglobulin levels previously to RTX use in order to establish an etiologic relationship with RTX and a quick diagnosis of antibody deficiency. The substitutive treatment with gammaglobulin seems to be useful in patients with severe or recurrent infections.

Disseminated bronchiectasis in an adult with common variable immunodeficiency / Bronquiectasias diseminada en un adulto con inmunodeficiencia común variable

Primary immunodeficiencies (PID) are traditionally considered childhood diseases; however, adults account for 35% of all patients with PID. Antibody deficiencies, especially Common Variable Immunodeficiency (CVID), which have their peak incidence in adulthood, require a high suspicion index. Even though the estimated frequency of CVID is not high (1:25,000), high rates of under diagnosis and under reporting are very likely. The delay in diagnosis increases the morbidity and mortality; therefore, adult physicians should be able to suspect, identify and initiate management of individuals with PID. Here we report the case of a 37 year-old man presenting to the emergency room with dyspnea, fever and cough; he developed respiratory failure requiring mechanical ventilation. He complained of recurring pneumonia associated with widespread bronchiectasis since he was 18 years old. Serum immunoglobulins quantification showed severe hypogammaglobulinemia (total IgG <140 mg/dL; total IgA, 2.9 mg/dL; and total IgM <5 mg/dL). Treatment with Human Intravenous Immunoglobulin (IVIG) 10% was started, and with antibiotic treatment for severe pneumonia (during 14 days) was also prescribed. His clinical evolution has been favorable after one year follow-up. Common Variable Immunodeficiency (CVID) diagnosis was made.

Las inmunodeficiencias primarias (IDP) son patologías que tradicionalmente se consideran de la niñez sin embargo los adultos representan el 35% del total de pacientes con IDP. Las deficiencias de anticuerpos, en especial la Inmunodeficiencia Común Variable (IDCV) tienen su pico de incidencia en la edad adulta, requiere un alto índice de sospecha y si bien su frecuencia estimada no es alta (1:25,000), es muy posible que el subregistro y subdiagnóstico si lo sean. El retraso en el diagnóstico aumenta la morbi-mortalidad razón por la cual los médicos de adultos deben estar en capacidad de sospechar, identificar e iniciar el manejo de las personas con IPD. Presentamos el caso de un hombre de 37 años de edad atendido en la sala de urgencias con disnea, fiebre y tos, desarrolla falla respiratoria requiriendo ventilación mecánica. Refería neumonías a repetición desde los 18 años de edad asociadas con bronquiectasias generalizadas. La cuantificación de inmunoglobulinas séricas evidenció hipogammaglobulinemia severa (IgG total <140 mg/dL, IgA total 2.9 mg/dL, IgM total <5 mg/dL), se inició inmunoglobulina humana endovenosa (IGIV) al 10%, y recibió tratamiento antibiótico por 14 dias para neumonía severa, su evolución clínica ha sido favorable hasta ahora (un año de seguimiento), se estableció el diagnostico de Inmunodeficiencia Común Variable (IDCV).

Giant Thymolipoma – A Rare Benign Tumour of the Thymus Gland

Thymolipoma is a rare benign tumour of mediastinum. It is often asymptomatic but can enlarge significantly prior to the diagnosis. It consists of thymic and fatty tissue surrounded by a capsule. A 23-year-old man sought medical attention for respiratory distress since 10 years progressively increasing in severity. Computed tomography findings were suggestive of a space occupying lesion in the anterior mediastinum with extension into hemi-thorax on either side. The tumour was surgically resected by median sternotomy. The tumour measured ∼21x25x10 cm and weighed 2800 gm. Histopathological examination revealed thymolipoma.

Opportunistic lung infections as a manifestation of Good's syndrome

Good's syndrome is an acquired immunodeficiency state associated with thymoma. It is characterized by recurrent infection, autoimmune disease, and immunologic abnormality. The insufficient immunity can be managed by intravenous immunoglobulin (IVIG) replacement therapy. We describe 2 patients who presented with Pneumocystis jiroveci pneumonia and Cytomegalovirus pneumonia after thymectomy for a thymoma. Immunologic study revealed hypogammaglobulinemia with very low B-cell count, consistent with Good's syndrome. They were successfully treated with trimethoprim/sulfamethoxazole and gancyclovir respectively, and they are all well without additional infections, receiving regular IVIG replacement.

Three cases report and literature review of X-Linked agammaglobulinemia / 临床儿科杂志

Objective To analyze the clinical features, diagnosis and treatment of X-Linked Agarnmaglobulinemia (XLA). Methods Clinical features, cellular and humoral immune functions, treatment and prognosis from 3 patients with XLA were retrospectively reviewed. Results The age of onset were from 11 months to 6 years in these 3 cases, however, the median age of diagnosis was 12 years. All patients showed multiple recurrent bacterial infections, arthritis involved large joints such as knee, ankle, elbow and hip. Laboratory examination revealed the decrease of serum gammmaglohulin and absence of B lymphocytes in the peripheral blood. All 3 patients were identiifed BTK mutations, which were frameshift mutation and nonsense mutation in exon 3, frameshift mutation in exon 10, missense mutation in exon 18. After XLA was diagnosed, the patients were managed by intravenous gammagloulin (IVIG) replacement. The non-steroidal anti-inflammatory drugs (NSAIDs) were administrated in patients combined arthritis. The small dose of hormones had been applied. All patients had a significantly improvement. Conclusions The clinical features of XLA have greater variability, with recurrent bacterial infections. Markedly decreased and absent tosils and lymph nodes, serum immunoglobulin may be one of the warning signs for early diagnosis of XLA. IVIG and NSAIDs can be jointly treatment of XLA with arthritis. The steroid and immunosuppressant agents should be used with caution.

Eventos adversos en 1395 infusiones con diferentes preparados de gammaglobulina intravenosa / Adverse events in 1395 infusions with different intravenous gammaglobulin products

Los procesos de aislamiento y esterilización de la gammaglobulina endovenosa (IVIG) afectan las características del producto terminado y, por lo tanto, su tolerabilidad. Distintos productos tienen diferentes incidencias de reacciones adversas. Este trabajo cuantifica los eventos adversos (EA) inmediatos provocados por distintas preparaciones de IVIG. Analizamos 1395 infusiones en 28 pacientes, con una mediana de 32.5 por sujeto (rango 2-214), utilizando seis preparados distintos de IVIG, con una dosis total promedio de 40.3 ± 8.3 g. Analizamos retrospectivamente 1 031 infusiones y 364 prospectivamente. Los pacientes utilizaron una media de 2.68 ± 1.8 IVIG diferentes, con una mediana de 2 (rango 1-6) por persona. El número de marcas comerciales utilizadas se relacionó con el número de infusiones recibidas, r = 0.73. En 24 (2.3%) de 1031 infusiones analizadas en forma retrospectiva se registraron EA que afectaron a 11 de los 23 casos incluidos, con una media de 2.18 ± 1.08 EA por afectado. De 24 pacientes y de 364 infusiones prospectivas, en 14 pacientes y en 32 (7.2%) procedimientos se observaron EA. Veinticuatro (42.9%) de 56 EA fueron leves, 31 (55.5%) moderados y uno (1.8%) fue grave. La velocidad de infusión fue de 9.04 ± 4.6 g/h para las que presentaron EA vs. 10.6 ± 4.6 g/h para las que no (p = 0.31). La incidencia, la gravedad y la proporción de pacientes afectados con EA para cada marca comercial de IVIG fueron muy diferentes entre sí. Esta información debe ser tomada en cuenta en el momento de selección de la IVIG a utilizar.

The processes of isolation and sterilization of intravenous gamma globulin (IVIG) affect the end product characteristics and, therefore, its tolerability. Different products have different incidences of adverse reactions. The aim of this study was to quantify the immediate adverse events (AE) caused by the different IVIG preparations. We analyzed 1 395 infusions in 28 patients, with a median of 32.5 per subject (range 2-214), using six different IVIG preparations, with an average dose 40.3 ±8.3 g. One thousand and thirty-one infusions were analyzed retrospectively and 364 prospectively. Patients used a mean of 2.68 ±1.8 different IVIGs, with a median of 2 (range 1-6) per person. The number of trademarks used was related to the number of infusions received, r = 0.73. AE presented in 24 (2.3%) of 1 031 infusions retrospectively analyzed, affecting 11 of 23 patients enrolled, with a mean of 2.18 ± 1.08 AE per subject. Of 24 patients and 364 infusions prospectively analyzed, AE were observed in 14 patients and in 32 (7.2%) procedures. Twenty-four (42.9%) of 56 AE were mild, 31 (55.5%) moderate and one (1.8%) severe. The infusion rate was 9.04±4.6 g/h for those presenting AE vs. 10.6±4.6 g/h for those who did not (p = 0.31, NS). The incidence, severity and proportion of patients with AE for each brand of IVIG were very different from each other. This information should be taken into account when selecting the IVIG to be used.

Inmunodeficiencia común variable: Epidemiología y manifestaciones clínicas en 69 pacientes / Common variable immunodeficiency: Epidemiology and clinical manifestations in 69 patients

La inmunodeficiencia común variable (IDCV) se caracteriza por una alteración en la producción de anticuerpos y una mayor susceptibilidad a infecciones por bacterias extracelulares capsuladas, principalmente del tracto respiratorio. Analizamos las características clínicas de 69 pacientes, evaluados en un período de 10 años en tres centros de la ciudad de Buenos Aires. Al inicio del estudio se encontraban en seguimiento 14 pacientes y al finalizar 60; la mayoría fueron derivados por infecciones o hipogammaglobulinemia, y casi la mitad con diagnóstico establecido de inmunodeficiencia. Sesenta y cinco (94.2%) pacientes presentaron infecciones por gérmenes capsulados, cuatro (6.1%) sepsis y dos tuberculosis. La edad promedio de comienzo de los síntomas infecciosos fue de 18.1 años, la edad promedio al momento del diagnóstico fue de 29.6 años y el retraso diagnóstico de 11.9 años. En 41 (59.4%) pacientes se registró el antecedente de diarreas recurrentes o crónicas. En 22 (31.9%) se diagnosticaron 13 enfermedades autoinmunes, siendo las más frecuentes las hematológicas y el hipotiroidismo. Ocho pacientes tuvieron linfoproliferación policlonal histológica, cuatro (5.8%) como enfermedad granulomatosa de hígado, laringe y piel, y cuatro como neumonía intersticial linfoidea (NIL). Diecinueve (27.5%) pacientes presentaron esplenomegalia y 23/57 (40.3%) imágenes sugestivas de procesos granulomatosos o linfocíticos en la TAC de tórax (incluidos los 4 con NIL). Tres (4.3%) pacientes desarrollaron linfoma B, cuatro (5.8%) adenocarcinoma de estómago y uno cáncer de mama. El estudio tuvo una mediana de seguimiento de 54 meses, rango 1-353 y durante el período del mismo murieron cuatro pacientes (5.8%).

Common variable immunodeficiency (CVID) is characterized by an impaired antibody production and an increased susceptibility to recurrent infections of the respiratory tract, mainly by extracellular encapsulated bacteria. We analyzed the clinical characteristics of 69 patients evaluated over a period of 10 years at three centers in the city of Buenos Aires. At the onset of the study 14 patients were on follow up, and at its end the number of patients reached to 60. Most of them consulted for infection or hypogammaglobulinemia and nearly half had an established diagnosis of immunodeficiency. Sixty-five (94.2%) patients had infections by encapsulated bacteria, four (6.1%) sepsis and two tuberculosis. The average age of onset of infectious symptoms was 18.1 years; the average age at diagnosis was 29.6 years and the delay to diagnosis 11.9 years. Forty one (59.4%) patients reported a history of recurrent or chronic diarrhea. In 22 (31.9%) 13 autoimmune diseases were diagnosed, being the most frequent the hematological disorders and hypothyroidism. Eight patients had histological polyclonal lymphoproliferation, four (5.8%) with granulomatous disease affecting the liver, the larynx and/or the skin; and four as lymphoid interstitial pneumonitis (LIP). Nineteen (27.5%) patients had splenomegaly and 23/57 (40.3%) images suggestive of lymphocytic or granulomatous processes (including the 4 with LIP) in the chest CT. Three (4.3%) patients developed B cell lymphoma, four (5.8%) stomach adenocarcinoma and one breast cancer. The study had a median follow-up of 54 months, range 1-353 and four patients (5.8%) died during the follow up.

Osteoarthritis of Hip in a Hypogammaglobulinemia Patient / 대한정형외과학회잡지

Hypoglobulinemia is characterized by functional or quantitative abnormalities of one or more components of the immune system. It is typically manifests as recurrent infections that usually start in childhood. These recurrent infections cause various clinical symptoms. Infectious or aseptic arthritis can develop, and especially in bone and joint abnormalities. No case of arthritis in a patients with hypogammaglobulinemia has been reported, so we report on the management of osteoarthritis of the hip in a hypogammaglobulinemia patient.

Hipogammaglobulinemia congénita asociada con trastornos de los granulocitos.: Presentación de un caso / Congenital hypogammaglobulinemia associated with granulocyte disorders.: A case presentation

Se reporta el caso de un niño de 11 meses de edad con historia de sepsis generalizada por Pseudomona aeruginosa a los 5 meses, neutropenia, leucopenia, anemia asociada con la sepsis y desde entonces, infecciones respiratorias agudas recurrentes del tracto respiratorio superior, manifestaciones alérgicas y forunculosis por pseudomona. El estudio inmunológico realizado mostró cifra disminuida de IgG con ligero incremento de IgM y valores normales de IgA y de la población de células B CD19+, así como disminución de la subpoblación de células T cooperadoras CD4+. Se encontró, además, neutropenia y defecto marcado de la fagocitosis. Se estableció el diagnóstico de hipogammaglobulinemia congénita asociada con trastornos de los granulocitos. El paciente recibió tratamiento con gammaglobulina humana por vía intramuscular, factor de transferencia e inmunoferón, con mejoría clínica evidente.

This is the case of a child aged 11 months with a history of systemic sepsis from Pseudomona aeruginosa at 5 months, neutropenia, leucopenia, sepsis-associated anemia and from then, recurrent acute respiratory infections of the high respiratory tract, allergic manifestations and furunculosis from pseudomona. Immunologic study conducted showed a decreased figure of IgG with a light increase of CD4+ cooperative-IgM of T cells. Also, we found the presence of neutropenia and marked defect of phagocytosis. We made the diagnosis of granulocyte-associate congenital hypogammaglobulinemia. The patient was treated with human gamma globulin by intramuscular route, transference factor and immunoferon, with an obvious improvement.

Carpal Tunnel Syndrome in Children with Hypogammaglobulinemia: Case Report / 대한정형외과학회잡지

Carpal tunnel syndrome occurs infrequently in children. Genetic disorders and systemic disease of carpal tunnel syndrome may be the predisposing factors for carpal tunnel syndrome in children. Immunoglobulins (Ig) play a major role in adaptive immunity, and the loss of certain species of immunoglobulin is known to increase the risk of certain types of infection. Patients with hypogammaglobulinemia have an increased risk of cellulitis, arthritis and osteomyelitis. We describe the management of bilateral carpal tunnel syndrome in children with hypogammaglobulinemia.

Massive Empyema Associated With Transient Hypogammaglobulinemia of Infancy and IgA Deficiency

Transient hypogammaglobulinemia of infancy (THI) is originally defined as a physiological maturation defect of immunoglobulin G (IgG) production that occurs at 3-6 months of age and lasts until 18 to 36 months of age. We report here on a 22-month-old child with THI and IgA deficiency, who had massive pneumococcal empyema. Her depressed IgG level returned to normal within 6 months, but IgA level was still low at 6 yr of age. Although THI is an age-dependent and self-limiting disorder, severe infection that includes an atypical presentation of an infection may occur in some patients and this requires evaluation with immunologic study.

A Case of Good's Syndrome / 감염과화학요법

Good's syndrome is the association of thymoma with immunodeficiency, characterized by hypogammaglobulinemia, B-cell lymphopenia and variably defects in cellular immunity with CD4+ T-cell lymphopenia and an inverted CD4+:CD8+ T-cell ratio. We report a 43-year-old male patient who presented with a 18-month history of productive cough and postnasal drip. One year ago, he underwent the operation for resection of a thymoma. Despite of appropriate management, sinusitis relapsed multiple times. He was found to have hypogammaglobulinemia with nearly absent B cells(4/microliter). The CD4+ T-cell count was 554/microliter with an inverted CD4+:CD8+ T-cell ratio of 0.6. His symptoms and signs improved with antibiotic treatment and monthly administration of intravenous immunoglobulin (IVIG, 400 mg/kg).

A Case of Good's Syndrome / 감염과화학요법

Good's syndrome is the association of thymoma with immunodeficiency, characterized by hypogammaglobulinemia, B-cell lymphopenia and variably defects in cellular immunity with CD4+ T-cell lymphopenia and an inverted CD4+:CD8+ T-cell ratio. We report a 43-year-old male patient who presented with a 18-month history of productive cough and postnasal drip. One year ago, he underwent the operation for resection of a thymoma. Despite of appropriate management, sinusitis relapsed multiple times. He was found to have hypogammaglobulinemia with nearly absent B cells(4/microliter). The CD4+ T-cell count was 554/microliter with an inverted CD4+:CD8+ T-cell ratio of 0.6. His symptoms and signs improved with antibiotic treatment and monthly administration of intravenous immunoglobulin (IVIG, 400 mg/kg).

A Case of Group O Losing Anti-B Selectively / 대한수혈학회지

We report a case of group O losing anti-B selectively. A 25-year-old male donated blood; on the donor test an ABO discrepancy was noted, and a further evaluation study was performed. ABO genotyping with an allele specific polymerase chain reaction assay revealed O/O and DNA sequencing of exons 6 and 7 of the ABO gene showed O01/O02. The serum gammaglobulin level was decreased and only 0.2% CD19 pan-B positive lymphocytes were present in a subset of lymphocytes. In a previous donor study, anti-B of the patient was lost from a third donor study and was still not detected.